From JK Henrickson at Beckman-Coulter: We have several customers who want to perform the ex vivo heparin therapeutic range study for their partial thromboplastin time (PTT) heparin assay, however, their institution does not have these types of patients very often. Is there a commercial source for heparinized plasmas, specifically unfractionated heparin?
Hello, and thank you for your question. To establish a local therapeutic range using the ex vivo (Brill-Edwards) method, the laboratory must assay at least 50 specimens from patients on unfractionated heparin (UFH) whose prothrombin times (PTs) are normal, plus 20 normal specimens. For smaller acute care facilities, it is difficult to locate 50 or more specimens that meet this criterion, yet we are required to run the curve with each change in reagent, reagent lot number, or instrument. To make matters worse, CAP prohibits in vitro spiking of plasmas as an alternative to the Brill-Edwards method.
Unfortunately, none of the commercial vendors has developed a set of UFH plasmas, so we are forced to do this on our own. I suspect vendors have done some market studies and determined they would lose money. Further, few institutions like to share patient specimens as their risk managers contemplate the possibility of viral transmission, though this may be OK within an affiliated health care system.
The best advice I have heard is to review PTT specimens daily, select the ones with heparin (prolonged PTTs) and normal PTs, presumably at the start of warfarin therapy, aliquot and freeze. Hopefully, over a year’s time the laboratory would accumulate enough specimens to run the curve, but they would need to continue this practice indefinitely.
An alternative, which I suspect you have discussed with your clients, is to bypass the PTT altogether and just set up the anti-Xa heparin assay, which is more accurate and reproducible. The additional cost becomes easier to justify when you add in the number of patients now receiving low molecular weight heparin or synthetic pentasaccharides who require laboratory monitoring. They need to be able to do the anti-Xa anyway to develop their Brill-Edwards curve.
This may not be the answer you are looking for, but maybe you can persuade Beckman-Coulter/IL to develop a set of calibrators. The trouble is, we are continuing to move towards new anticoagulants like rivaroxaban that can’t be measured using the PTT, so I suspect your R&D folks would see little future in it.
I wonder if anyone out there has an alternative approach to finding specimens for developing the PTT therapeutic range?